Professor, Molecular Microbiology and Immunology, Keck School of Medicine
Molecular Microbiology & Immunology
Keck School of Medicine
- Hepatitis Viruses
Research OverviewHepatitis B virus (HBV) and hepatitis C virus (HCV) can both cause severe liver diseases including hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). The research of our laboratory is focused on the molecular and cellular biology of these two clinically important viruses. Our research goal is to understand the replication and pathogenesis of these two viruses.
HBV has a circular 3.2 Kb DNA genome that contains four overlapping transcription units. An ongoing research project of this laboratory is to understand how these four transcription units communicate with each other for their expressions. Recent studies of ours indicate that the HBV X protein is an auxiliary factor for HBV replication and oncogenesis. We are also interested in understanding the interactions between HBV and its host. Our recent studies indicated that HBV could induce autophagy to enhance its replication and that androgen could enhance HBV replication and hepatocarcinogenesis. We also discovered that HBV could use the host interferon response to stimulate its gene expression and replication. Experiments are in progress to further understand how HBV interacts with its host cells to facilitate its replication and pathogenesis.
HCV is an RNA virus. The genome of this virus encodes a polyprotein, which is cleaved by viral and cellular proteases to generate at least ten viral gene products. We have recently discovered a novel HCV protein named F protein. This protein is encoded by an alternative reading frame. We are currently investigating the molecular mechanism that regulates the expression of this F protein and its biological functions. In addition, we have also discovered that HCV can induce ER stress and the unfolded protein response to perturb the autophagic pathway. We found that HCV could induce the accumulation of autophagosomes and use them as the platform for its RNA replication. Our recent research also indicated that HCV could perturb many cellular signaling pathways to enhance its entry, replication and release. The persistent induction of ER stress and the long-term perturbation of autophagy and cellular signaling pathways likely play an important role in HCV pathogenesis and carcinogenesis. Experiments are in progress to further study the interaction between HCV and its host cells to understand the life cycle of HCV.